Two continual retinal tumor cell lines (RAO 188 from rat and UAL 1-3 from mouse) have been established in our laboratory and are being used for in vitro and in vivo experiments. The objectives of these studies are (a) to test the hypothesis that urinary concentrations of vanilmandelic acid and homovanillic acid (the main breakdown products of catecholamine) reflect degrees of retinal tumor cell differentiation, and (b) to develop reliable criteria for the effectiveness of currently available anticancer agents. During the first year of work, we have investigated the course of maturation in retinoblastoma cells to establish background data for our planned studies. Our specific aim has been to determine what triggers dedifferentiation of the cells. We found that exposure of undifferentiated RAO 188 cells to cAMP analogs (DBcAMP and 8-BrcAMP) caused cell growth to cease and decreased DNA and RNA synthesis. This effect became irreversible after a period of 10 days exposure to the drugs. This finding will be used in our in vivo experiments. That is, before transplanting RAO 188 cells into animals (for studies of catecholamine metabolism), the cells will be incubated with cAMP analog for 10 days to ensure that they will remain differentiated in the animal system.